INDIANAPOLIS Scientists have deciphered the structure of an essential part of Mediator, a complex molecular machine that plays a vital role in regulating the transcription of DNA.
The research adds an important link to discoveries that have enabled scientists to gain a deeper understanding of how cells translate genetic information into the proteins and processes of life. The findings, published in the July 3 advance online issue of the journal Nature, were reported by a research team led by Yuichiro Takagi, Ph.D., assistant professor of biochemistry and molecular biology at Indiana University School of Medicine.
The fundamental operations of all cells are controlled by the genetic information the genes stored in each cell's DNA, a long double-stranded chain. Information copied from sections of the DNA through a process called transcription leads to synthesis of messenger RNA, eventually enabling the production of proteins necessary for cellular function. Transcription is undertaken by the enzyme called RNA polymerase II.
As cellular operations proceed, signals are sent to the DNA asking that some genes be activated and others be shut down. The Mediator transcription regulator accepts and interprets those instructions, telling RNA polymerase II where and when to begin the transcription process.
Mediator is a gigantic molecular machine composed of 25 proteins organized into three modules known as the head, the middle, and the tail. Using X-ray crystallography, the Takagi team was able to describe in detail the structure of the Mediator Head module, the most important for interactions with RNA polymerase II.
"It's turned out to be extremely novel, revealing how a molecular machine is built from multiple proteins," said Takagi.
"As a molecular machine, the Mediator head module needs to have elements of both stability and flexibility in order to accommodate numerous interactions. A portion of the head
|Contact: Eric Schoch|
Indiana University School of Medicine